METHOD AND DEVICE FOR PRODUCING 99mTc

ABSTRACT

A method for producing  99m Tc may include: providing a solution comprising  100 Mo-molybdate-ions; providing a proton beam having an energy suitable for inducing a  100 Mo (p, 2n)  99m Tc-nuclear reaction when exposing  100 Mo-molybdate-ions; exposing the solution to the proton beams and inducing a  100 Mo (p, 2n)  99m Tc-nuclear reaction; and applying an extraction method for extracting the  99m Tc from the solution. Further, a device for producing  99m Tc may include: a solution with  100 Mo-molybdate-ions; an accelerator for providing a proton beam with energy which is suitable for inducing a  100 Mo (p, 2n)  99m Tc-nuclear reaction when exposing  100 Mo-molybdate-ions, for exposing the solution and for inducing a  100 Mo (p, 2n)  99m Tc-nuclear reaction; and an extraction step for extracting  99m Tc from the solution.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a U.S. National Stage Application of InternationalApplication No. PCT/EP2011/050728 filed Jan. 20, 2011, which designatesthe United States of America, and claims priority to DE PatentApplication No. 10 2010 006 435.1 filed Feb. 1, 2010. The contents ofwhich are hereby incorporated by reference in their entirety.

TECHNICAL FIELD

This disclosure relates to a method and a device for producing ^(99m)TC.^(99m)TC is used, inter alia, in medical imaging, for example in SPECTimaging.

BACKGROUND

A commercially available ^(99m)TC generator is an instrument forextracting the metastable isotope ^(99m)Tc from a source which containsdecaying ⁹⁹Mo.

⁹⁹Mo in turn is usually obtained from a method which uses highlyenriched uranium ²³⁵U as a target. ⁹⁹Mo is created as a fission productby irradiating the target with neutrons. However, as a result ofinternational treaties, it will become ever more difficult in future tooperate reactors with highly enriched uranium, which could lead toshortages in the supply of radionuclides for SPECT imaging.

SUMMARY

In one embodiment, a method for producing ^(99m)TC may comprise:providing a solution with ¹⁰⁰Mo -molybdate ions, providing a proton beamwith an energy suitable for inducing a ¹⁰⁰Mo (p, 2 n) ^(99m)Tc nuclearreaction when ¹⁰⁰Mo-molybdate ions are irradiated, irradiating thesolution with the proton beam and inducing a ¹⁰⁰Mo (p, 2 n) ^(99m)Tcnuclear reaction, and applying an extraction method for extracting the^(99m)Tc from the solution.

In a further embodiment, the extraction method is a solvent extractionmethod, more particularly using methyl ethyl ketone. In a furtherembodiment, the dissolved ¹⁰⁰Mo-molybdate ions remaining after the^(99m)Tc extraction are returned to the solution to be irradiated. In afurther embodiment, the solution with ¹⁰⁰Mo-molybdate ions is a solutionof a ¹⁰⁰Mo-molybdate salt, wherein a nuclear reaction which leads to atleast one cation end product is induced in the solution by irradiationwith the proton beam at the cations of the ¹⁰⁰Mo-molybdate salt. In afurther embodiment, after extracting the ^(99m)Tc, the remaining,dissolved ¹⁰⁰Mo-molybdate ions are returned to the irradiating solutionand the at least one cation end product is removed before the supply,more particularly by using an ion exchanger. In a further embodiment,after extracting the ^(99m)Tc from the solution, the extracted ^(99m)Tcis cleansed of impurities resulting from the cation end product, moreparticularly by using an ion exchanger. In a further embodiment, the¹⁰⁰Mo-molybdate salt comprises ⁶Li₂ ¹⁰⁰MoO₄, and wherein the at leastone cation end product comprises ³H. In a further embodiment, theMo-molybdate salt comprises Na₂ ¹⁰⁰MoO₄, and wherein the cation endproduct comprises ¹⁸F. In a further embodiment, the ¹⁰⁰Mo-molybdate saltcomprises K₂ ¹⁰⁰MoO₄, and wherein the cation end

product comprises Ca ions.

In another further embodiment, a device for producing ^(99m)Tc maycomprise: a solution with ¹⁰⁰Mo-molybdate ions, an accelerator forproviding a proton beam with an energy suitable for inducing a ¹⁰⁰Mo (p,2n) ^(99m)Tc nuclear reaction when ¹⁰⁰Mo-molybdate ions are irradiated,for irradiating the solution and for inducing a ¹⁰⁰Mo (p, 2n) ^(99m)Tcnuclear reaction, and an extraction stage for extracting the ^(99m)Tcfrom the solution.

In a further embodiment, the dissolved ¹⁰⁰Mo-molybdate ions remainingafter the ^(99m)Tc extraction can be returned to the solution to beirradiated by a loop. In a further embodiment, the solution with¹⁰⁰Mo-molybdate ions is a solution of a ¹⁰⁰Mo-molybdate salt, wherein anuclear reaction which leads to at least one cation end product isinduced in the solution by irradiation with the proton beam at thecations of the ¹⁰⁰Mo-molybdate salt. In a further embodiment, the deviceadditionally has a first cleaning stage downstream of the extractionstage, in which cleaning stage the extracted ^(99m)Tc can be cleansed ofimpurities resulting from the cation end product. In a furtherembodiment, the device additionally has a second cleaning stage, inwhich the at least one cation end product is removed, more particularlyby using an ion exchanger, before the remaining, dissolved¹⁰⁰Mo-molybdate ions are supplied to the solution to be irradiated.

BRIEF DESCRIPTION OF THE DRAWINGS

Example embodiments will be explained in more detail below withreference to FIGS., in which:

FIG. 1 shows the design of a device for producing ^(99m)Tc from alithium-molybdate salt, according to one embodiment,

FIG. 2 shows the design of a device for producing ^(99m)Tc from asodium-molybdate salt, according to one embodiment, and

FIG. 3 shows the design of a device for producing ^(99m)Tc from apotassium-molybdate salt, according to one embodiment.

DETAILED DESCRIPTION

Some embodiment provide a method and a device for the alternativeproduction of ^(99m)Tc.

For example, in some embodiments a method for producing ^(99m)TCcomprises:

-   -   providing a solution with ¹⁰⁰Mo -molybdate ions, providing a        proton beam with an energy suitable for inducing a ¹⁰⁰Mo (p, 2n)        ^(99m)Tc nuclear reaction when ¹⁰⁰Mo-molybdate ions are        irradiated,    -   irradiating the solution with the proton beam and inducing a        ¹⁰⁰Mo (p, 2n) ^(99m)Tc nuclear reaction,    -   applying an extraction method for extracting the ^(99m)Tc from        the solution.

Thus, the ^(99m)Tc is obtained directly on the basis of a nuclearreaction which occurs as a result of the interaction of the proton beamwith the molybdenum atoms, according to the equation ¹⁰⁰Mo (p, 2n)^(99m)Tc. The energy of the proton beam is greater than 20 MeV and istherefore in a range in which the effective cross section for theaforementioned nuclear reaction lies. As a result, ^(99m)Tc atoms can beobtained in a number that is sufficient for the production of ^(99m)Tc.As a result of the fact that the molybdenum atoms are present asmolybdate ions in a solution, the resultant ^(99m)Tc can subsequently beextracted from the solution in a simple manner with the aid of anextraction method. The extracted ^(99m)Tc can then be used for differentpurposes, in particular for producing a radionuclide for SPECT imaging.

The proton beam is accelerated to an energy of at least 20 MeV. Theparticle beam may be accelerated to an energy of 20 MeV to 25 MeV.Restricting the maximum energy to no more than 35 MeV, more particularlyto 30 MeV and most particularly to 25 MeV avoids nuclear reactionsleading to undesired reaction products, e.g. Tc isotopes other than^(99m)Tc, being triggered as a result of a particle beam with too highan energy, which would then again require an additional step by means ofwhich the undesired reaction products are removed again. The chamber inwhich the solution with molybdate ions is contained can be designed ordimensioned such that the emerging particle beam has an energy of atleast 10 MeV. In this manner, the energy range of the proton beam can bekept in a range in which the occurring nuclear reactions remaincontrollable and in which undesired reaction products merely occur to anacceptable extent.

Accelerating protons to the aforementioned energy usually requires onlya single accelerator unit of average size, which can also be installedand used locally. Using the above-described method, ^(99m)Tc can beproduced locally in the vicinity or in the surroundings of the desiredlocation of use, for example in a hospital environment. In contrast toconventional, non-local production methods which are accompanied by theuse of large installations such as in nuclear reactors and thedistribution problems connected therewith, local production solves manyproblems. Nuclear medicine units can plan their workflows independentlyfrom one another and are not reliant on complex logistics andinfrastructure.

In one embodiment, the extraction method can be a liquid-liquidextraction method, more particularly using methyl ethyl ketone.

This extraction method is suitable because ^(99m)Tc is present in asolution. The ^(99m)Tc dissolves in methyl ethyl ketone, with themolybdate ions continuing to remain in the aqueous solution. This makesit possible to separate the ^(99m)Tc from the ¹⁰⁰Mo. The ^(99m)Tc-loadedmethyl ethyl ketone can e.g. be dried such that the ^(99m)Tc cansubsequently be used e.g. for producing a radiopharmaceutical.

In one embodiment, the dissolved ¹⁰⁰Mo-molybdate ions remaining afterthe ^(99m)Tc extraction can be returned to the solution to beirradiated, for example in a closed loop. This may ensure that theparent material, namely the ¹⁰⁰Mo-molybdate ions, is used particularlyefficiently.

In one embodiment, the solution with ¹⁰⁰Mo -molybdate ions is a solutionof a ¹⁰⁰Mo-molybdate salt, wherein a nuclear reaction which leads to atleast one cation end product is induced in the solution by irradiationwith the proton beam at the cations of the ¹⁰⁰Mo-molybdate salt, saidreaction more particularly leading to a cation end product, which wasnot present in the original solution to be irradiated, which is an ionwhich is unstable and/or which is potentially harmful to the human body.The term “cation end product” does not necessarily mean that the endproduct has to be a cation, it merely denotes the fact that the endproduct originates from the cations of the salt.

In this case, the remaining, dissolved ¹⁰⁰Mo-molybdate ions can bereturned to the irradiating solution after extracting the ^(99m)Tc,wherein the at least one cation end product is removed before thesupply, more particularly by using an ion exchanger.

This embodiment can be advantageous in that the solution returned to thesolution to be irradiated contains no constituents which, in the case ofrenewed irradiation by the proton beam, would lead to furtherirradiation products that differ from the cation end products. By way ofexample, it is then possible to avoid cation end products being suppliedto the solution which, in the case of irradiation, would lead tofurther, new nuclear reactions. This makes it possible to avoiduncontrolled or unmanageable nuclear reactions despite the return of themolybdate ions.

In one embodiment, the extracted ^(99m)Tc can be cleansed of impuritiesresulting from the cation end product, more particularly by using an ionexchanger.

This makes it possible, for example, to remove potentially undesiredconstituents of the extracted ^(99m)Tc solution before furtherprocessing. Thus, for example, it is possible to remove potentialsubstances which are toxic to the human body prior to the production ofthe radionuclide or other radionuclides with a different half-life.

In one embodiment variant, the ¹⁰⁰Mo-molybdate salt comprises ⁶Li₂¹⁰⁰MoO₄. ⁶Li decays by the nuclear reaction ⁶Li(p, 3He)⁴H to ⁴H, whichin turn immediately decays to tritium.

If ⁷Li were used, the bombardment by the proton beam would trigger thereaction ⁷Li(p, n)⁷Be, with the ⁷Be having to be removed again. The useof ⁶Li avoids this.

As a result of this, no cation end product is created which, in the caseof renewed irradiation by the proton beam, would lead to an uncontrolledchain of nuclear reactions. The cleaning stage, by means of which thecation end product being created is removed, can optionally be dispensedwith.

In another embodiment variant, the ¹⁰⁰Mo-molybdate salt comprises Na₂¹⁰⁰MoO₄. Here, the at least one cation end product comprises F.Naturally occurring Na is converted into Mg by bombardment with theproton beam as a result of the reaction ²³Na (p, n) ²³Mg, with said ²³Mgin turn quickly decaying to ²³Na. A further nuclear reaction is ²³Na(p,x)¹⁸F. Overall, ¹⁸ F is now also present as a cation end product afterthe irradiation, said ¹⁸F not having been present in the originalsolution. The ¹⁸F can be removed with the aid of an ion exchanger, forexample from the solution which contains the ^(99m)Tc after theextraction of ^(99m)Tc or from the solution which contains the remainingmolybdate after the extraction of ^(99m)Tc and which is returned to theoriginal solution. As a result, this avoids the irradiation of ¹⁸F andthe return loop triggering a chain of nuclear reactions which aredifficult to control.

In a further embodiment variant, the ¹⁰⁰Mo-molybdate salt comprises K₂¹⁰⁰MoO₄, with the cation end product comprising ⁴¹Ca. Naturallyoccurring ⁴¹K is converted by the proton beam in the following nuclearreactions: ⁴¹K (p, n) ⁴¹Ca, ⁴¹K (p, γ) ⁴²Ca, ⁴¹K(p, αγ) ³⁸Ar. ³⁹ K,which likewise occurs naturally, is converted by the proton beam in thefollowing nuclear reactions: ³⁹K(p, d)³⁸K, ³⁹K (p, γ) ⁴⁰Ca. ³⁸K decaysto ³⁸Ar. Of all the Ca ions created, only ⁴¹Ca is unstable. All ions canbe removed by the ion exchanger. Returning ³⁸Ar is uncritical becausethe interaction cross section for the interaction with the proton beamis in a different region than the interaction cross section for the¹⁰⁰Mo (p, 2n) ^(99m)Tc nuclear reaction. Returning and irradiating ³⁸Artherefore does not create a nuclear reaction chain with uncontrollableend products.

In some embodiments, a device for producing ^(99m)Tc comprises:

-   -   a solution with ¹⁰⁰Mo-molybdate ions,    -   an accelerator for providing a proton beam with an energy        suitable for inducing a ¹⁰⁰Mo (p, 2n) ^(99m)Tc nuclear reaction        when ¹⁰⁰Mo-molybdate ions are irradiated, for irradiating the        solution and for inducing a ¹⁰⁰Mo (p, 2n) ^(99m)Tc nuclear        reaction,    -   an extraction stage for extracting the ^(99m)Tc from the        solution.

In one embodiment variant, the solution with ¹⁰⁰Mo-molybdate ions is asolution of a ¹⁰⁰Mo-molybdate salt, wherein a nuclear reaction whichleads to at least one cation end product is induced in the solution byirradiation with the proton beam at the cations of the ¹⁰⁰Mo-molybdatesalt and wherein the device additionally has a first cleaning stagedownstream of the extraction stage, in which cleaning stage theextracted ^(99m)Tc can be cleansed of impurities resulting from thecation end product.

In one embodiment variant, provision is made for a loop, by means ofwhich the dissolved ¹⁰⁰Mo-molybdate ions of the solution to beirradiated, which remain after the extraction of ^(99m)Tc, can beresupplied, for example via a closed loop. More particularly, if thesolution with ¹⁰⁰Mo-molybdate ions is a solution of a ¹⁰⁰Mo-molybdatesalt, the device can additionally have a cleaning stage, interposed intothe loop, in which the at least one cation end product is removed, moreparticularly by using an ion exchanger, before the remaining, dissolved¹⁰⁰Mo-molybdate ions are supplied.

According to the embodiment of FIG. 1, an aqueous solution 11 isinitially provided, in which ⁶Li₂ ¹⁰⁰MoO₄ is dissolved.

The solution 11 is subsequently routed to an irradiation chamber 13,which is irradiated by a proton beam 15 which is generated by anaccelerator unit 17 such as e.g. a cyclotron. Here, the proton beam 15has an energy of 20 to 25 MeV on entry into the irradiation chamber 13,and an energy of approximately 10 MeV upon exit. In this energy range,the proton beam 15 interacts with the ¹⁰⁰Mo and partly converts thelatter directly into ^(99m)Tc in a nuclear reaction, on the basis of thenuclear reaction ¹⁰⁰Mo (p, 2n) ^(99m)Tc.

As a result of irradiating the ⁶Li ions, the following nuclear reactionsalso occur: ⁶Li(p, 3He)⁴H, with ⁴H immediately decaying to tritium.

The irradiated solution is routed to a chamber 19 for solventextraction, in which the ^(99m)Tc is extracted from the aqueous solutionwith the aid of MEK (methyl ethyl ketone). The ^(99m)Tc dissolved in MEKcan then be processed further, for example in a subsequentpharmaceutical module (not illustrated).

The remaining solution of the molybdate salt is returned to theoriginally provided solution 11.

The embodiment in FIG. 2 differs from FIG. 1 by virtue of the fact thatan aqueous solution 21 is initially provided, in which Na₂ ¹⁰⁰MoO₄ isdissolved.

As a result of irradiating the Na ions, the following nuclear reactionsoccur: ²³Na(p, n) ²³Mg and ²³Na(p, x) ¹⁸F. ²³Mg in turn decays to stable²³Na. By contrast, ¹⁸F is radioactive.

The irradiated solution is routed to a chamber 19 for solventextraction, in which the ^(99m)Tc is extracted from the aqueous solutionwith the aid of MEK (methyl ethyl ketone) . Prior to further processing,impurities resulting from the ¹⁸F can be removed with the aid of a firstion exchanger 23.

¹⁸F can likewise be removed with the aid of a further ion exchanger 25,before the solution of the molybdate salt remaining after the ^(99m)Tcextraction is returned to the originally provided solution 21.

The extracted ^(99m)Tc solution 27, which has been cleansed of ¹⁸F, canthen for example be made available in a subsequent pharmaceuticalmodule.

The embodiment in FIG. 3 differs from FIG. 1 by virtue of the fact thatan aqueous solution 31 is initially provided, in which K₂ ¹⁰⁰MoO₄ isdissolved.

As a result of irradiating the K ions, the following nuclear reactionsoccur: ⁴¹K (p, n) ⁴¹Ca, ⁴¹K (p, γ) ⁴²Ca, ⁴¹K (p, αγ) ³⁸Ar, ³⁹K (p, d)³⁸K, ³⁹K (p, γ)⁴⁰Ca. Of all the cation end products which are beingcreated, only ⁴¹Ca is unstable.

The irradiated solution is routed to a chamber 19 for solventextraction, in which the ^(99m)Tc is extracted from the aqueous solutionwith the aid of MEK (methyl ethyl ketone).

Prior to further processing, impurities resulting from the ⁴¹Ca can beremoved with the aid of a first ion exchanger 33.

The ⁴¹Ca and the other Ca ions can likewise be removed with the aid of afurther ion exchanger 35 before the solution of the molybdate saltremaining after the ^(99m)Tc extraction is returned to the originallyprovided solution 31.

The extracted ^(99m)Tc solution, which has been cleansed of ⁴¹Ca, canthen for example be dried in a dryer unit 37 and be made available in asubsequent pharmaceutical module (not illustrated).

LIST OF REFERENCE SIGNS

-   11, 21, 31 Aqueous solution-   13 Irradiation chamber-   15 Proton beam-   17 Accelerator unit-   19 Chamber for solvent extraction-   23, 33 First ion exchanger-   25, 35 Further ion exchangers-   27 Cleansed ^(99m)Tc solution 27-   29 Dryer device

1. A method for producing ^(99m)TC, comprising: providing a solution comprising ¹⁰⁰Mo-molybdate ions, providing a proton beam having an energy suitable for inducing a ¹⁰⁰Mo (p, 2n) ^(99m)Tc nuclear reaction when ¹⁰⁰Mo-molybdate ions are irradiated, irradiating the solution with the proton beam and inducing a ¹⁰⁰Mo (p, 2n) ^(99m)Tc nuclear reaction, applying an extraction method to extract the ^(99m)Tc from the solution.
 2. The method of claim 1, wherein the extraction method comprises a solvent extraction method.
 3. The method of claim 1, comprising returning the dissolved ¹⁰⁰Mo-molybdate ions remaining after the ^(99m)Tc extraction to the solution to be irradiated.
 4. The method of claim 1, wherein the solution with ¹⁰⁰Mo-molybdate ions is a solution of a ¹⁰⁰Mo-molybdate salt and wherein a nuclear reaction which leads to at least one cation end product is induced in the solution by irradiation with the proton beam at the cations of the ¹⁰⁰Mo-molybdate salt.
 5. The method of claim 4, comprising after extracting the ^(99m)Tc, returning the remaining dissolved ¹⁰⁰Mo-molybdate ions to the irradiating solution and removing the at least one cation end product before the supply.
 6. The method of claim 4, comprising after extracting the ^(99m)Tc from the solution, cleansing the extracted ^(99m)Tc of impurities resulting from the cation end product.
 7. The method of claim 4, wherein the ¹⁰⁰Mo-molybdate salt comprises ⁶Li₂ ¹⁰⁰MoO₄, and wherein the at least one cation end product comprises ³H.
 8. The method of claim 4, wherein the ¹⁰⁰Mo-molybdate salt comprises Na₂ ¹⁰⁰MoO₄, and wherein the cation end product comprises ¹⁸F.
 9. The method of claim 4, wherein the ¹⁰⁰Mo-molybdate salt comprises K₂ ¹⁰⁰MoO₄, and wherein the cation end product comprises Ca ions.
 10. A device for producing ^(99m)Tc, a solution comprising ¹⁰⁰Mo-molybdate ions, an accelerator configured to provide a proton beam having an energy suitable for inducing a ¹⁰⁰Mo (p, 2n) ^(99m)Tc nuclear reaction when ¹⁰⁰Mo-molybdate ions are irradiated, for irradiating the solution, and for inducing a ¹⁰⁰Mo (p, 2n) ^(99m)Tc nuclear reaction, and an extraction stage configured to extract the ^(99m)Tc from the solution.
 11. The device of claim 10, configured to return the dissolved ¹⁰⁰Mo-molybdate ions remaining after the ^(99m)Tc extraction to the solution to be irradiated by a loop.
 12. The device of claim 10, wherein the solution with ¹⁰⁰Mo-molybdate ions is a solution of a ¹⁰⁰Mo-molybdate salt, and wherein a nuclear reaction which leads to at least one cation end product is induced in the solution by irradiation with the proton beam at the cations of the ¹⁰⁰Mo-molybdate salt.
 13. The device of claim 12, further comprising a first cleaning stage downstream of the extraction stage and configured to cleanse the extracted ^(99m)Tc of impurities resulting from the cation end product.
 14. The device of claim 12, further comprising a second cleaning stage configured to remove the at least one cation end product before the remaining, dissolved ¹⁰⁰Mo-molybdate ions are supplied to the solution to be irradiated.
 15. The method of claim 1, wherein the extraction method comprises a solvent extraction method using methyl ethyl ketone.
 16. The method of claim 4, comprising after extracting the ^(99m)Tc, returning the remaining dissolved ¹⁰⁰Mo-molybdate ions to the irradiating solution and removing the at least one cation end product using an ion exchanger.
 17. The method of claim 4, comprising after extracting the ^(99m)Tc from the solution, using an ion exchanger to cleanse the extracted ^(99m)Tc of impurities resulting from the cation end product. 